Tissue engineering is a potentially powerful method to treat diabetes, heart failure and liver disease. Present tissue engineering approaches generally involve seeding cells onto biodegradable polymeric scaffolds. Current limitations with tissue engineering scaffolds include their inability to generate vascularized tissues, uniformly seed cells throughout the constructs, or mimic the complex cellular microenvironment. We hypothesize that by using the principles of life science, biomaterials science, and microengineering, it will be possible to develop 3D tissue-engineered constructs with controlled microvasculature and tissue architecture. We intend to use cell-laden hydrogels for fabricating microengineered tissue constructs, and to examine the functionality and applicability of these constructs by using cadiomyocytes as a tissue model. We propose a 3-step strategy to accomplish this task. Firstly, we will develop novel hydrogels comprised of natural and biodegradable materials with improved mechanical properties and favorable to cell-encapsulation. Then, we will investigate approaches to engineer the microvasculature within these hydrogels by fabricating an interconnected network of microchannels and macropores. Lastly, we will incorporate additional complexity into the cell-laden hydrogels to generate 3D tissues and replicate the cellular microenvironment. The specific aims of our project are: 1. To develop methods for fabricating biodegradable hydrogels with controlled mechanical, chemical and biological properties for microscale tissue engineering applications; 2. To engineer tissue constructs using cell-laden hydrogels incorporated with a microvasculature comprising of an interconnected network of microchannels and macropores; 3. To engineer biological complexity within the microfabricated cell-laden scaffolds to generate functional 3D cardiac tissue constructs. Public Health Relevance Statement (provided by applicant): The development of a novel microscale 3D vascularized tissue engineered constructs have tremendous potential applications in the treatment of many different disease, including heart diseases. We will develop 3D tissues using novel hydrogels and provide vasculature to supply nutrients to the engineered tissue.